Randomized Trial to Assess PO Versus IV Antibiotics (POvIV)

A Prospective Randomized Trial to Assess PO Versus IV Antibiotics for the Treatment of Post-op Wound Infection After Extremity Fractures (POvIV)

The goal of this study is to evaluate the effect of treatment of post-op wound infection in long bones after fracture fixation or joint fusion and either: (Group 1) operative debridement and PO antibiotic treatment for 6 weeks; or (Group 2) operative debridement and IV antibiotics for 6 weeks.

Primary Hypothesis 1: The rate of study injury related surgical interventions by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 1: The rate of treatment failure by one year in Group 1 will be non-inferior to the rate in Group 2. Treatment failure is defined as wound problems that require surgery >2 weeks after initial debridement, infection recurrence, infection with a new pathogen, joint erosion, implant failure, medical problems related to the treatment administration which necessitates a switch from one arm to the other.

Secondary Hypothesis 2: The rate of re-hospitalization for complications, infection, non-union and amputation by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 3: Following discharge for treatment of infection, per patient treatment costs at 1 year will be lower in Group 1 than in Group 2.

Secondary Hypothesis 4: Adherence in Group 1 will be non-inferior to adherence in Group 2.

Secondary Hypothesis 5: Patient satisfaction with treatment in Group 1 will be non-inferior to adherence in Group 2.

Specific Aim 2: To build and validate a risk prediction model for failure of treatment of early post-op wound infections after fixation of fractures and joint fusions.

Study Overview

• Status: Completed
• Conditions: Wound Infection
• Intervention / Treatment: Other: PO versus IV antibiotics Route of administration evaluation

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States
      • Cedars Sinai Medical Center
    • San Francisco, California, United States
      • University of California at San Francisco
  • Colorado
    • Denver, Colorado, United States
      • Denver Health and Hospital Authority
  • Florida
    • Miami, Florida, United States
      • University of Miami Ryder Trauma Center
  • Indiana
    • Indianapolis, Indiana, United States
      • Eskenazi Health
  • Iowa
    • Iowa City, Iowa, United States
      • University of Iowa Hospitals & Clinics
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland R Adams Cowley Shock Trauma Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States
      • St. Louis University Medical Center
  • New York
    • Jamaica, New York, United States
      • Jamaica Hospital Medical Center
    • New York, New York, United States
      • NYU Langone Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States
      • Carolinas Medical Center
    • Winston-Salem, North Carolina, United States
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States
      • MetroHealth Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • Penn State University M.S. Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • San Antonio, Texas, United States
      • San Antonio Military Medical Center (SAMMC)
  • Virginia
    • Charlottesville, Virginia, United States
      • University of Virginia
    • Falls Church, Virginia, United States
      • Inova Fairfax Hospital
    • Portsmouth, Virginia, United States
      • Naval Medical Center Portsmouth
  • Washington
    • Seattle, Washington, United States
      • University of Washington/Harborview Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with any fractures of any bone at or proximal to and including the tarsal/metatarsal joint (Lisfranc) or proximal to the carpal joints (includes distal radius fractures), excluding the spine, treated with any type of internal fixation, or
2. Patients undergoing fusion of any bone at or proximal to and including the subtalar joint or radial carpal joint, (excluding the spine) that develop a post op wound infection at any time.

3. Patients diagnosed with a wound infection of the study injury, defined as patients with at least one of the following:

   1. Deep culture positive after operative debridement.
   2. Cultures positive in thio only after operative debridement.
   3. Negative culture after operative debridement if wound infection meets the Center for Disease control and Prevention (CDC) criteria.
4. Patients who are English or Spanish competent.
5. Patients aged 18 - 84.
6. Patients with bacteria susceptible to both PO and IV antibiotics.
7. Patients able to be treated for their infection at the METRC facility for at least 12 months following definitive surgical procedure
8. Patients may have multiple eligible study-eligible injuries.
9. Patients may have temporary external fixation prior to definitive fixation.
10. Patients may have received antibiotics prior to operative wound debridement.
11. Patient is able to obtain study medication(s).
12. Patient may be pregnant at the time of screening.

Exclusion Criteria:

1. Patients who have high risk of amputation of the study limb (based on opinion of the initial managing physician).
2. Patients undergoing treatment with any other investigational therapy within the month preceding implantation or planned within the 12 months following implantation.

3. Patients with history of chronic infection at the site of study injury, defined as:

   patients with chronic osteomyelitis identified by radiographic erosion or sequestrum; or patients with more than one instance of surgical treatment of infection and approximately 6 week course of antibiotics.

4. Patients with pathological fractures; a known history of Paget's disease.
5. Patients for whom the definitive treatment of the study injury was an external fixator.
6. Patients who are currently on Selective Serotonin Reuptake Inhibitor (SSRI) medication (e.g. Zoloft, Prozac, Celexa), and bacteria is MRSA
7. Patients with cultures positive in thio only.
8. Patients who are incarcerated or who have unstable housing situations due to concerns regarding ability to receive home care, adherence phone calls, and maintain follow up. .
9. Patients or designated proxy who are unwilling to provide consent.
10. Patients with a history of IV drug use who in the investigator's opinion are unsuitable candidates for IV therapy.
11. Patients likely to have severe problems maintaining follow-up, including patients diagnosed with a severe psychiatric conditions, patients who live too far outside the hospital's catchment area.
12. Patients with traumatic brain injury or who are intellectually challenged and who lack adequate family support to ensure adherence to the protocol.
13. Patients unable to swallow oral medications or without adequately functioning GI tract.
14. Patients who, based upon the clinical judgment of the treating clinician, are NOT equally suited for treatment with either oral or intravenous antibiotics (i.e., those for whom there is a clinical treatment preference).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Oral Antibiotic; Oral Antibiotic Arm; Participants assigned to this group will receive oral antibiotics as prescribed by their treating physician.	Other: PO versus IV antibiotics Route of administration evaluation; This is a study of oral (per os, (PO)) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after fixation of fractures and joint fusions. This is not a study of an experimental drug but a study of route of administration of standard use antibiotics. Antibiotic regimen options decision will be made by the Study Surgeon at each site in consult with local Infectious Disease experts based on local standard practices and bacterial susceptibilities.; Other Names: based on local practices and bacterial susceptibilities
ACTIVE_COMPARATOR: IV Antibiotic; Participants assigned to this group will receive intravenous (IV) antibiotics as prescribed by their treating physician.	Other: PO versus IV antibiotics Route of administration evaluation; This is a study of oral (per os, (PO)) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after fixation of fractures and joint fusions. This is not a study of an experimental drug but a study of route of administration of standard use antibiotics. Antibiotic regimen options decision will be made by the Study Surgeon at each site in consult with local Infectious Disease experts based on local standard practices and bacterial susceptibilities.; Other Names: based on local practices and bacterial susceptibilities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Study injury related surgical interventions by 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure by 1 year	Treatment failure is defined as wound problems that require surgery >2 weeks after initial debridement, infection recurrence, infection with a new pathogen, joint erosion, implant failure, medical problems related to the treatment administration which necessitates a switch from one arm to the other.	1 year
Re-hospitalizations by 1 year	Re-hospitalization for complications, such as infection, non-union and amputation	1 year
Healthcare costs	Cost of PO versus IV medications include medical record and bill abstracted costs associated with outpatient clinic visits, home health visits, medication, subsequent hospital readmission, and other types of medical care as identified over the course of the study.	1 year
Medication Adherence	Patient adherence to PO and IV medications Patient adherence with PO antibiotics will be monitored through wireless-enabled microchip monitors embedded in pill bottles by the Medication Event Monitoring System (MEMS) and weekly adherence questionnaire.	1 year
Satisfaction with treatment	Patient satisfaction with treatment measured by Short Form Patient Satisfaction Questionnaire (PSQ-18) The PSQ-18 measures 6 domains: technical quality, interpersonal manner, communication, financial aspects of care, time spent with doctor, and accessibility. A score of 0.8 or higher in each domain correlates with improved satisfaction.	1 year

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Investigators: Study Director: Tara Taylor, MPH, Johns Hopkins Bloomberg School of Public Health; Principal Investigator: William T Obremskey, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 3, 2013
• Primary Completion (ACTUAL): September 30, 2019
• Study Completion (ACTUAL): December 30, 2020

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (ESTIMATE): October 26, 2012

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Wound infection; Oral Antibiotic; Intravenous Antibiotic
• Additional Relevant MeSH Terms: Infections; Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: METRC POvIV